Blockwise Stochastic Variance-Reduced Methods with Parallel Speedup for Multi-Block Bilevel Optimization

In this paper, we consider non-convex multi-block bilevel optimization (MBBO) problems, which involve $m\gg 1$ lower level problems and have important applications in machine learning. Designing a stochastic gradient and controlling its variance is more intricate due to the hierarchical sampling of blocks and data and the unique challenge of estimating hyper-gradient. We aim to achieve three nice properties for our algorithm: (a) matching the state-of-the-art complexity of standard BO problems with a single block; (b) achieving parallel speedup by sampling $I$ blocks and sampling $B$ samples for each sampled block per-iteration; (c) avoiding the computation of the inverse of a high-dimensional Hessian matrix estimator. However, it is non-trivial to achieve all of these by observing that existing works only achieve one or two of these properties. To address the involved challenges for achieving (a, b, c), we propose two stochastic algorithms by using advanced blockwise variance-reduction techniques for tracking the Hessian matrices (for low-dimensional problems) or the Hessian-vector products (for high-dimensional problems), and prove an iteration complexity of $O(\frac{m\epsilon^{-3}\mathbb{I}(I<m)}{I\sqrt{I}} + \frac{m\epsilon^{-3}}{I\sqrt{B}})$ for finding an $\epsilon$-stationary point under appropriate conditions. We also conduct experiments to verify the effectiveness of the proposed algorithms comparing with existing MBBO algorithms

On-chip black hole: Hawking radiation and curved spacetime in a superconducting quantum circuit with tunable couplers

Hawking radiation is one of quantum features of a black hole, which can be understood as a quantum tunneling across the event horizon of the black hole, but it is quite difficult to directly observe the Hawking radiation of an astrophysical black hole. Remarkable experiments of analogue black holes on various platforms have been performed. However, Hawking radiation and its quantum nature such as entanglement have not been well tested due to the experimental challenges in accurately constructing curved spacetime and precisely measuring the thermal spectrum. Based on the recent architecture breakthrough of tunable couplers for superconducting processor, we realize experimentally an analogue black hole using our new developed chip with a chain of 10 superconducting transmon qubits with interactions mediated by 9 transmon-type tunable couplers. By developing efficient techniques to engineer the couplings between qubits via tuning couplers, we realize both the flat and curved spacetime backgrounds. The quantum walks of quasi-particle in the curved spacetime reflect the gravitational effect around the black hole, resulting in the behavior of Hawking radiation. By virtue of the state tomography measurement of all 7 qubits outside the analogue event horizon, we show that Hawking radiation can be verified. In addition, an entangled pair is prepared inside the horizon and the dynamics of entanglement in the curved spacetime is directly measured. Our results would stimulate more interests to explore information paradox, entropy and other related features of black holes using programmable superconducting processor with tunable couplers.Comment: modified manuscripts, 7 pages, 4 figures (main text) + 12 pages (supplementary information

Nonlinear Drift Resonance Between Charged Particles and Ultralow Frequency Waves: Theory and Observations

In Earth’s inner magnetosphere, electromagnetic waves in the ultralow frequency (ULF) range play an important role in accelerating and diffusing charged particles via drift resonance. In conventional drift resonance theory, linearization is applied under the assumption of weak waveâ particle energy exchange so particle trajectories are unperturbed. For ULF waves with larger amplitudes and/or durations, however, the conventional theory becomes inaccurate since particle trajectories are strongly perturbed. Here we extend the drift resonance theory into a nonlinear regime, to formulate nonlinear trapping of particles in a waveâ carried potential well, and predict the corresponding observable signatures such as rolledâ up structures in particle energy spectrum. After considering how this manifests in particle data with finite energy resolution, we compare the predicted signatures with Van Allen Probes observations. Their good agreement provides the first observational evidence for the occurrence of nonlinear drift resonance, highlighting the importance of nonlinear effects in magnetospheric particle dynamics under ULF waves.Plain Language SummaryIn Earth’s Van Allen radiation belts, ultralow frequency (ULF) waves in the frequency range between 2 and 22 mHz play a crucial role in accelerating charged particles via a resonant process named drift resonance. When such a resonance occurs, a resonant particle observes a constant phase of the wave electric field, and it experiences a net energy excursion. In previous studies of drift resonance, a linearization approach is often applied with assumption of a weak waveâ particle energy exchange. In this study, we extend the linear theory into the nonlinear regime to formulate the particle behavior in the ULF wave field, and predict characteristic signatures of the nonlinear process observable from a virtual magnetospheric spacecraft. Such newly predicted signatures are found to agree with observations from the National Aeronautics and Space Administration’s Van Allen Probes, which provides the first identification of nonlinear drift resonance and highlights the importance of nonlinear effects in ULF waveâ particle interactions in the Van Allen radiation belts.Key PointsThe nonlinear theory of ULF waveâ particle drift resonance is developed to formulate the behavior of charged particles in ULF wave fieldSignatures of nonlinear drift resonance include rolledâ up structures and/or multiperiod oscillations in the particle energy spectrumIn situ observations of the newly predicted signatures validate the theory and provide a first identification of nonlinear drift resonancePeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146432/1/grl57916_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146432/2/grl57916.pd

Tirofiban for Stroke without Large or Medium-Sized Vessel Occlusion

The effects of the glycoprotein IIb/IIIa receptor inhibitor tirofiban in patients with acute ischemic stroke but who have no evidence of complete occlusion of large or medium-sized vessels have not been extensively studied. In a multicenter trial in China, we enrolled patients with ischemic stroke without occlusion of large or medium-sized vessels and with a National Institutes of Health Stroke Scale score of 5 or more and at least one moderately to severely weak limb. Eligible patients had any of four clinical presentations: ineligible for thrombolysis or thrombectomy and within 24 hours after the patient was last known to be well; progression of stroke symptoms 24 to 96 hours after onset; early neurologic deterioration after thrombolysis; or thrombolysis with no improvement at 4 to 24 hours. Patients were assigned to receive intravenous tirofiban (plus oral placebo) or oral aspirin (100 mg per day, plus intravenous placebo) for 2 days; all patients then received oral aspirin until day 90. The primary efficacy end point was an excellent outcome, defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. Secondary end points included functional independence at 90 days and a quality-of-life score. The primary safety end points were death and symptomatic intracranial hemorrhage. A total of 606 patients were assigned to the tirofiban group and 571 to the aspirin group. Most patients had small infarctions that were presumed to be atherosclerotic. The percentage of patients with a score of 0 or 1 on the modified Rankin scale at 90 days was 29.1% with tirofiban and 22.2% with aspirin (adjusted risk ratio, 1.26; 95% confidence interval, 1.04 to 1.53, P = 0.02). Results for secondary end points were generally not consistent with the results of the primary analysis. Mortality was similar in the two groups. The incidence of symptomatic intracranial hemorrhage was 1.0% in the tirofiban group and 0% in the aspirin group. In this trial involving heterogeneous groups of patients with stroke of recent onset or progression of stroke symptoms and nonoccluded large and medium-sized cerebral vessels, intravenous tirofiban was associated with a greater likelihood of an excellent outcome than low-dose aspirin. Incidences of intracranial hemorrhages were low but slightly higher with tirofiban

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke

Importance It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023.InterventionsEligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability.Trial RegistrationChiCTR.org.cn Identifier: ChiCTR210005172

GlPRMT5 inhibits GlPP2C1 via symmetric dimethylation and regulates the biosynthesis of secondary metabolites in Ganoderma lucidum

Abstract PRMT5, a type II arginine methyltransferase, is involved in transcriptional regulation, RNA processing and other biological processes and signal transduction. Secondary metabolites are vital pharmacological compounds in Ganoderma lucidum, and their content is an important indicator for evaluating the quality of G. lucidum. Here, we found that GlPRMT5 negatively regulates the biosynthesis of secondary metabolites. In further in-depth research, GlPP2C1 (a type 2C protein phosphatase) was identified out as an interacting protein of GlPRMT5 by immunoprecipitation-mass spectrometry (IP-MS). Further mass spectrometry detection revealed that GlPRMT5 symmetrically dimethylates the arginine 99 (R99) and arginine 493 (R493) residues of GlPP2C1 to weaken its activity. The symmetrical dimethylation modification of the R99 residue is the key to affecting GlPP2C1 activity. Symmetrical demethylation-modified GlPP2C1 does not affect the interaction with GlPRMT5. In addition, silencing GlPP2C1 clearly reduced GA content, indicating that GlPP2C1 positively regulates the biosynthesis of secondary metabolites in G. lucidum. In summary, this study reveals the molecular mechanism by which GlPRMT5 regulates secondary metabolites, and these studies provide further insights into the target proteins of GlPRMT5 and symmetric dimethylation sites. Furthermore, these studies provide a basis for the mutual regulation between different epigenetic modifications

The Relationship of Family Functioning and Suicidal Ideation among Adolescents: The Mediating Role of Defeat and the Moderating Role of Meaning in Life

Objective: To investigate the relationship between family functioning and suicidal ideation among adolescents. Method: A total of 4515 junior and senior high school students were assessed using the Family APGAR, the Depressive Symptom Index-Suicidality Subscale, the Defeat Scale, and the Chinese Meaning in Life Questionnaire. Results: This study found pairwise correlations between suicidal ideation, family functioning, defeat, and meaning in life. Specifically, family functioning was an influencing factor of adolescent suicidal ideation, and defeat was a mediator of the relationship between family functioning and adolescent suicidal ideation; meaning in life was found to be a moderator of the first half of the mediation process by defeat, that is, it moderated the influence of family functioning on adolescent defeat. Conclusions: This study demonstrated that the relationship between family functioning and adolescent suicidal ideation, as well as the influence of defeat and meaning in life on this relationship, constituted a moderated intermediary model. This finding has both theoretical and practical value for the implementation of a psychosocial model of adolescent suicide prevention and intervention